Melchior F

References (2)

Title : A Novel SUMO1-specific Interacting Motif in Dipeptidyl Peptidase 9 (DPP9) That Is Important for Enzymatic Regulation - Pilla_2012_J.Biol.Chem_287_44320
Author(s) : Pilla E , Moller U , Sauer G , Mattiroli F , Melchior F , Geiss-Friedlander R
Ref : Journal of Biological Chemistry , 287 :44320 , 2012
Abstract : Sumoylation affects many cellular processes by regulating the interactions of modified targets with downstream effectors. Here we identified the cytosolic dipeptidyl peptidase 9 (DPP9) as a SUMO1 interacting protein. Surprisingly, DPP9 binds to SUMO1 independent of the well known SUMO interacting motif, but instead interacts with a loop involving Glu(67) of SUMO1. Intriguingly, DPP9 selectively associates with SUMO1 and not SUMO2, due to a more positive charge in the SUMO1-loop. We mapped the SUMO-binding site of DPP9 to an extended arm structure, predicted to directly flank the substrate entry site. Importantly, whereas mutants in the SUMO1-binding arm are less active compared with wild-type DPP9, SUMO1 stimulates DPP9 activity. Consistent with this, silencing of SUMO1 leads to a reduced cytosolic prolyl-peptidase activity. Taken together, these results suggest that SUMO1, or more likely, a sumoylated protein, acts as an allosteric regulator of DPP9.
ESTHER : Pilla_2012_J.Biol.Chem_287_44320
PubMedSearch : Pilla_2012_J.Biol.Chem_287_44320
PubMedID: 23152501
Gene_locus related to this paper: human-DPP9

Title : The cytoplasmic peptidase DPP9 is rate-limiting for degradation of proline-containing peptides - Geiss-Friedlander_2009_J.Biol.Chem_284_27211
Author(s) : Geiss-Friedlander R , Parmentier N , Moller U , Urlaub H , Van den Eynde BJ , Melchior F
Ref : Journal of Biological Chemistry , 284 :27211 , 2009
Abstract : Protein degradation is an essential process that continuously takes place in all living cells. Regulated degradation of most cellular proteins is initiated by proteasomes, which produce peptides of varying length. These peptides are rapidly cleaved to single amino acids by cytoplasmic peptidases. Proline-containing peptides pose a specific problem due to structural constrains imposed by the pyrrolidine ring that prevents most peptidases from cleavage. Here we show that DPP9, a poorly characterized cytoplasmic prolyl-peptidase, is rate-limiting for destruction of proline-containing substrates both in cell extracts and in intact cells. We identified the first natural substrate for DPP9, the RU1(34-42) antigenic peptide (VPYGSFKHV). RU1(34-42) is degraded in vitro by DPP9, and down-regulation of DPP9 in intact cells results in increased presentation of this antigen. Together our findings demonstrate an important role for DPP9 in peptide turnover and antigen presentation.
ESTHER : Geiss-Friedlander_2009_J.Biol.Chem_284_27211
PubMedSearch : Geiss-Friedlander_2009_J.Biol.Chem_284_27211
PubMedID: 19667070
Gene_locus related to this paper: human-DPP9